944 F.3d 1327
Fed. Cir.2019Background
- Amgen sued Hospira for infringing two patents: the '298 patent (methods producing erythropoietin (EPO) isoforms and compositions having a "predetermined in vivo specific activity") and the '349 patent (cells producing specified units of EPO measured by radioimmunoassay).
- At a 2017 jury trial, the jury found the asserted claims of the '298 patent infringed and not invalid, found the asserted claims of the '349 patent not infringed and not invalid, awarded Amgen $70 million, and found 7 of 21 accused Hospira batches covered by the §271(e)(1) Safe Harbor while 14 were not.
- The district court denied Hospira’s and Amgen’s post-trial JMOL and new-trial motions; both parties appealed adverse rulings (Hospira challenging infringement, invalidity, Safe Harbor instructions/findings, and damages; Amgen cross-appealing denial of JMOL/new trial on the '349 patent).
- Technical issues in dispute included the meaning of an "isolated biologically active erythropoietin isoform" and whether claim 27 requires separately prepared isoforms or permits mixtures prepared by ion-exchange chromatography, the scope of §271(e)(1) Safe Harbor as to manufacture versus use and per-batch analysis, and whether dot-blot assay data in Hospira’s BLA could be converted to RIA units to show infringement of the '349 patent.
- The Federal Circuit affirmed the district court on all contested points: claim construction and infringement/noninvalidity of claim 27 of the '298 patent; Safe Harbor instructions and the jury’s per-batch Safe Harbor findings; admissibility of Amgen’s damages expert and the $70M award; and the denial of JMOL and new trial on the '349 patent.
Issues
| Issue | Amgen's Argument (Plaintiff) | Hospira's Argument (Defendant) | Held |
|---|---|---|---|
| Construction of claim 27 (whether "isoforms of claim 1" must be separately prepared/isolated before mixing) | Claim 27 does not require separate preparation; "preparing a mixture" is broader than physically mixing isolated fractions. | Claim 27 requires isolating individual isoforms and then recombining; district court’s construction reads out "isolated." | Affirmed district court: claim 27 need not require separately preparing isolated isoforms; specification discloses simultaneous isolation and preparation of mixtures. |
| Infringement of claim 27 ('298 patent) | Evidence (BLA, expert testimony) shows Hospira’s product meets claim 1 limits and has a predetermined in vivo specific activity range; supports infringement. | Amgen failed to prove claim 1 limitations and predetermined in vivo activity; showing biosimilarity to Epogen is insufficient. | Substantial evidence supports jury verdict of infringement of claim 27; Amgen presented proof of claim-1 limitations and predetermined activity range. |
| Anticipation by Lai (invalidity of claim 27) | Lai’s Example 2 discloses ion-exchange elution producing mixtures with desired activity — anticipates claim 27. | Lai does not disclose EPO isoforms or predetermined in vivo specific activity; at best Hospira relies on inherency which it did not prove. | Affirmed: substantial evidence supports jury that Lai does not expressly or inherently anticipate claim 27. |
| Jury instructions on §271(e)(1) Safe Harbor (focus on manufacture vs use) | Instructions improperly focused on Hospira’s intent in manufacturing rather than whether the use of patented invention was reasonably related to FDA submissions. | The accused acts were Hospira’s manufacturing uses of Amgen’s claimed methods; instructions properly asked whether each act of manufacture was reasonably related to FDA submissions. | Affirmed: instructions legally correct — per-act (per-batch) evaluation of whether manufacture (the accused use) was reasonably related to FDA submissions; extraneous purposes do not defeat Safe Harbor if manufacture was so related. |
| Application of Safe Harbor to particular batches | All 21 batches were made for development or to respond to FDA (BLA/CRL), so all should be protected. | Some batches were commercial/CPV or post-approval-type activity not required for the original submissions; evidence supported treating batches separately. | Affirmed: substantial evidence supported jury’s finding that 14 batches were not solely reasonably related to FDA submissions (e.g., planned commercial inventory, CPV, optional stability testing). |
| Damages (admissibility of Dr. Heeb; lump-sum royalty) | Dr. Heeb’s lump-sum, value-of-delay methodology fairly modeled the hypothetical negotiation and was admissible; jury could award lump-sum without claw-back. | Methodology improperly measures Hospira’s potential gain and gives Amgen windfall; lump-sum without claw-back was speculative given no approval or sales at trial. | District court did not abuse discretion admitting Dr. Heeb; substantial evidence supports $70M award within experts’ ranges and jury’s discretion to choose lump-sum. |
| Infringement of '349 patent (conversion of dot-blot to RIA units) | Hospira’s BLA dot-blot data convert to >100 U thresholds (by Amgen’s expert) demonstrating infringement; Hospira offered no rebuttal. | Dot-blot and RIA are not comparable; Hospira’s expert explained dot-blot cannot reliably be converted to RIA units for unpurified material. | Affirmed: substantial evidence supported jury’s verdict of noninfringement; Hospira’s expert provided unrebutted reasons to reject conversion to RIA. |
Key Cases Cited
- Teva Pharm. USA, Inc. v. Sandoz, Inc., 574 U.S. 318 (2015) (claim construction standard: de novo review of legal questions and clear-error for subsidiary factual findings)
- Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) (intrinsic evidence primary in claim construction; limit reliance on extrinsic evidence)
- Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005) (§271(e)(1) Safe Harbor extends to all uses reasonably related to FDA submissions and requires per-activity evaluation)
- TransWeb, LLC v. 3M Innovative Props. Co., 812 F.3d 1295 (Fed. Cir. 2016) (standard for JMOL review)
- Koito Mfg. Co. v. Turn-Key-Tech, LLC, 381 F.3d 1142 (Fed. Cir. 2004) (anticipation is factual and reviewed for substantial evidence)
- Lucent Techs., Inc. v. Gateway, Inc., 580 F.3d 1301 (Fed. Cir. 2009) (standard for reviewing jury damages awards; award upheld absent gross excess or speculation)
- Amgen Inc. v. Int’l Trade Comm’n, 565 F.3d 846 (Fed. Cir. 2009) (pre-approval activity is not automatically within §271(e)(1); per-activity inquiry required)